SCGE

Text on blue background welcoming the National Academy of Engineering Class of 2026 with the NAE logo below.

This week, four members of the UC Berkeley community, including IGI Founder Jennifer Doudna, were elected to the National Academy of Engineering — one of the highest professional distinctions for engineers (and #bioengineers). Learn more: https://ow.ly/Zivp50YcAV6

TIME100 Health: Kiran Musunuru and Rebecca Ahrens-Nicklas Find out why they're on the TIME100 Health 2026 list.

Congrats to SCGE researchers Kiran Musunuru and Rebecca Ahrens-Nicklas for being named to the Time100 Most Influential People in Health list for 2026!

time.com/collections/...

Treatment of a severe vascular disease using a bespoke CRISPR-Cas9 base editor in mice Pathogenic missense mutations in the alpha actin isotype 2 gene (ACTA2) cause multisystemic smooth muscle dysfunction syndrome (MSMDS), a genetic vasculopathy that is associated with stroke, aortic dissection, and death in childhood. Here, we ...

Here, SCGE researchers perform mutation-specific protein engineering to develop a bespoke CRISPR-Cas9 enzyme with enhanced on-target activity against the most common MSMDS-causative mutation ACTA2 R179H.
pmc.ncbi.nlm.nih.gov/articles/PMC...

FDA Rare Disease Innovation Hub FDA created the Rare Disease Innovation Hub (the Hub) to serve as a point of collaboration and connectivity between CBER and CDER.

Gene Therapy News: FDA Rare Disease Innovation Hub 2026 Strategic Agenda is now available at www.fda.gov/industry/med...

Microfluidic Device Type Improves Heart mRNA Delivery In Vivo To improve lipid nanoparticle (LNP)-mediated delivery to nonliver tissues, scientists modify LNP chemistry or add targeting ligands. One underexplored alternative is to change the formulation process ...

Here, SCGE researchers report that an LNP formulated with a herringbone mixer led to 2-fold more heart delivery than the same LNP formulated with a bifurcating mixer. These data suggest that it is possible to increase heart delivery via nanoparticle processing. (2/2)
pubs.acs.org/doi/10.1021/...

Microfluidic Device Type Improves Heart mRNA Delivery In Vivo To improve lipid nanoparticle (LNP)-mediated delivery to nonliver tissues, scientists modify LNP chemistry or add targeting ligands. One underexplored alternative is to change the formulation process ...

To improve lipid nanoparticle (LNP)-mediated delivery to nonliver tissues, scientists modify LNP chemistry or add targeting ligands. One underexplored alternative is to change the formulation process that creates the LNP. (1/2)

3)And more!

View the platform website at scge.mcw.edu/platform/home

#RareDisease #Regulatory #GeneTherapy #FreeResource (3/3)

2) View documents generated through regulatory interactions between the U.S. Food and Drug Administration (FDA) and SCGE consortium projects. (2/3)

scge.mcw.edu/platform/pub...

Have you checked out the SCGE platform site? There is a lot of great information available!

1) Use the publicly accessible Gene Therapy Clinical Trial Browser to find information on gene therapy development from a variety of sources. (1/3)

scge.mcw.edu/platform/dat...

The Cas9-d system provides a versatile approach to adjust Cas9 levels, demonstrating its potential as an experimental tool for controlling genome editing outcomes in vitro and ex vivo. With further development, it holds promise for enhancing somatic cell genome editing in vivo. (2/2)

Controlling CRISPR-Cas9 genome editing in human cells using a molecular glue degrader Khajanchi and Saha present a small-molecule-controlled Cas9-degron (Cas9-d) system for reversible regulation of CRISPR genome editing in human cells. Used as an experimental in vitro tool, Cas9-d enab...

Here, SCGE researchers evaluate a novel molecular glue degradation system, called Cas9-degron (Cas9-d), designed to degrade Cas9 in the presence of the US Food and Drug Administration (FDA)-approved drug, pomalidomide (POM). (1/2)
www.cell.com/molecular-th...

Deadline: January 30 ⏱️ Don't miss out on the opportunity to present your groundbreaking work #ASGCT2026! Submit your abstract: https://annualmeeting.asgct.org/abstracts/submission-information

SCGE Meet the Expert Webinar Series Meet the Expert is a webinar series presented by the SCGE Consortium that aims to connect researchers with experts in the gene therapy space.

Meet the Expert is a webinar series held by the Somatic Cell Genome Editing (SCGE) consortium to connect with experts involved in different aspects of gene therapy development and regulatory approval. Find more Meet the Expert webinars at scge.mcw.edu/meet-the-exp... (3/3)

#GeneTherapy #Webinar

Andy Holt is the Chief Commercial Officer at Viralgen. Jacob Smith is the Head of Technical Development & CMC Strategy at Viralgen. (2/3)

YouTube video by SCGE Outreach Meet the Expert: Andy Holt and Jacob Smith

In this video of the SCGE Meet the Expert series, Andy Holt and Jacob Smith discuss AAV manufacturing and considerations for IND-enabling studies. (1/3)

Watch the full webinar at www.youtube.com/watch?v=fyCm...

Collectively, their results highlight inflammation-inducible IL-1-targeted therapy using an rAAV vector as a long-lasting, pathophysiologic treatment for chronic inflammatory diseases. (4/4)

#GeneTherapy #BiomedicalResearch #RheumatoidArthritis

The rheumatoid arthritis model mice showed a significant reduction in circulating immune cells, expression of the genes associated with inflammatory responses, joint swelling, and bone destruction. (3/4)

Nature-inspired IL-1 targeted therapy to treat chronic inflammatory diseases The interleukin (IL)-1 pathway is a key mediator of inflammation and innate immune responses. Its dysregulation contributes to rheumatoid arthritis (R…

In this study, SCGE researchers develop a recombinant adeno-associated virus (rAAV)-based gene therapy to deliver an inflammation-inducible, secreted human IL-1 receptor antagonist (sIL-1Ra) as a complementary approach to existing IL-1 blockers. (2/4)

www.sciencedirect.com/science/arti...

The interleukin (IL)-1 pathway is a key mediator of inflammation and innate immune responses. Its dysregulation contributes to rheumatoid arthritis and autoinflammatory diseases. (1/4)

⏱️ It's time to finalize your #ASGCT2026 abstract. Hit that submit button today! https://annualmeeting.asgct.org/abstracts/submission-information

A new review from the Doudna Lab lab on tissue-targeted in vivo delivery of gene editors: https://www.nature.com/articles/s41587-025-02945-w

#CRISPR #delivery

Gene Therapy News: Solid Biosciences Receives FDA Orphan Drug Designation for SGT-212 Dual-Route Gene Therapy for the Treatment of Friedreich’s Ataxia

investors.solidbio.com/news-release...

For Phase 2, the goal of the SCGE program is to accelerate the development of genome editing therapies into clinic.

There are many rare diseases being studied in the current phase of the program. Learn more about the different diseases being studied here: scge.mcw.edu/rare-diseases/

#RareDisease

Researchers from the SCGE Phase 1 Biological Effects Initiative published this review on monitoring biological effects of somatic cell genome editing. Read the publication at www.nature.com/articles/s41...

Thanks to everyone in the group who contributed!

#BiologicalEffects #GeneTherapy

These studies provide methods and reagents to precisely control the dosage and half-life of CRISPR-based technologies, propelling their therapeutic development. (5/5)

#CRISPR #biotech #GeneTherapy

Using pomalidomide, they were able to control the half-life of large CRISPR-based technologies and small anti-CRISPRs that inhibit such technologies, allowing them to build the first examples of on-switch for base editors. (4/5)

A Molecular Glue Approach to Control the Half-Life of CRISPR-Based Technologies Cas9 is a programmable nuclease that has furnished transformative technologies, including base editors and transcription modulators (e.g., CRISPRi/a), but several applications of these technologies, including therapeutics, mandatorily require precision control of their half-life. For example, such control can help avert any potential immunological and adverse events in clinical trials. Current genome editing technologies to control the half-life of Cas9 are slow, have lower activity, involve fusion of large response elements (>230 amino acids), utilize expensive controllers with poor pharmacological attributes, and cannot be implemented in vivo on several CRISPR-based technologies. We report a general platform for half-life control using the molecular glue, pomalidomide, that binds to a ubiquitin ligase complex and a response-element bearing CRISPR-based technology, thereby causing the latter’s rapid ubiquitination and degradation. Using pomalidomide, we were able to control the half-life of large CRISPR-based technologies (e.g., base editors and CRISPRi) and small anti-CRISPRs that inhibit such technologies, allowing us to build the first examples of on-switch for base editors. The ability to switch on, fine-tune, and switch-off CRISPR-based technologies with pomalidomide allowed complete control over their activity, specificity, and genome editing outcome. Importantly, the miniature size of the response element and favorable pharmacological attributes of the drug pomalidomide allowed control of activity of base editor in vivo using AAV as the delivery vehicle. These studies provide methods and reagents to precisely control the dosage and half-life of CRISPR-based technologies, propelling their therapeutic development.

SCGE researchers report a general platform for half-life control using the molecular glue, pomalidomide, that binds to a ubiquitin ligase complex and a response-element bearing CRISPR-based technology, causing the latter’s rapid ubiquitination and degradation. (3/5)
pubs.acs.org/doi/10.1021/...

A Molecular Glue Approach to Control the Half-Life of CRISPR-Based Technologies Cas9 is a programmable nuclease that has furnished transformative technologies, including base editors and transcription modulators (e.g., CRISPRi/a), but several applications of these technologies, including therapeutics, mandatorily require precision control of their half-life. For example, such control can help avert any potential immunological and adverse events in clinical trials. Current genome editing technologies to control the half-life of Cas9 are slow, have lower activity, involve fusion of large response elements (>230 amino acids), utilize expensive controllers with poor pharmacological attributes, and cannot be implemented in vivo on several CRISPR-based technologies. We report a general platform for half-life control using the molecular glue, pomalidomide, that binds to a ubiquitin ligase complex and a response-element bearing CRISPR-based technology, thereby causing the latter’s rapid ubiquitination and degradation. Using pomalidomide, we were able to control the half-life of large CRISPR-based technologies (e.g., base editors and CRISPRi) and small anti-CRISPRs that inhibit such technologies, allowing us to build the first examples of on-switch for base editors. The ability to switch on, fine-tune, and switch-off CRISPR-based technologies with pomalidomide allowed complete control over their activity, specificity, and genome editing outcome. Importantly, the miniature size of the response element and favorable pharmacological attributes of the drug pomalidomide allowed control of activity of base editor in vivo using AAV as the delivery vehicle. These studies provide methods and reagents to precisely control the dosage and half-life of CRISPR-based technologies, propelling their therapeutic development.

Current genome editing technologies to control the half-life of Cas9 are slow, have lower activity, involve fusion of large response elements, utilize expensive controllers with poor pharmacological attributes, and cannot be implemented in vivo on several CRISPR-based technologies. (2/5)

Cas9 is a programmable nuclease that has furnished transformative technologies, including base editors and transcription modulators, but several applications of these technologies, including therapeutics, mandatorily require precision control of their half-life. (1/5)

Happy to report that our paper on "Imaging CRISPR-edited CAR-T cell therapies with optical and PET reporters" has been published in Theranostics (IF 13.3) t.co/qTOWjGqssf. Huge thanks to co-first author Rafael Sánchez-Pupo, our mentor John Ronald and the rest of the team to get this over the line!